Amanda M. Shelby, RVT, VTS (A&A)

Jurox Animal Health, Inc. USARACE 931-32527 Category One: Scientific Veterinarians and Technicians

Current Non-Schedule II Drug Options and Applications for

Analgesia

COURSE OUTLINE

Part 1

Systemic Options

Injectable and Oral

Calculating CRIs

Part 2

Local Analgesics and Adjuvants

Methods and Calculations

Loco-Regional Techniques

Example protocols

WHY THE “SHORTAGE”?

*figures in kg of anhydrous acid or base

www.dea.gov/divisions/hq/2017/hq080417.shtml

Controlled Drug 2015 2016 2017 2018

Fentanyl 2,300.000 2,300.000 1350.000 1342.320

Hydromorphone 7000.000 7000.000 5140.800 4547.720

Methadone 31,875.000 31,875.000 23,700.000 22,278.000

Morphine 62,500.000 62,500.000 35,000.000 33,958.440

Oxymorphone 7,750.000 6,250.000 3,600.000 3,395.280

Sufentanil 6.255 6.255 4.000 1.880

COURSE OBJECTIVES

Unconsciousness

AnalgesiaMuscle relaxation

OpioidsNSAIDs,

Local Anesthetics,

NMDA antagonists,

Alpha2 agonists

And More!

Review Pain and its Impact

Provide Alternatives

Confidence to Effectively Administer

A REVIEW OF PAIN

Delayed wound healing

Increased infection

Delayed normalcy

Increased cost

Longer hospital

stay

PAIN

Unpleasant sensory or emotional

experience associated with actual or

potential tissue damage.

~International Association for the Study of Pain

THE ASSESSMENT OF PAIN

Continual reassessments

Glasgow Composite Measure

Pain Scale

Botucatu Multidimensional Pain

Scale (BMPS)

Colorado Pain Scale

Tranquilli, William J.; Grimm, Kurt A.; Lamong, Leigh A., Pain Management for the Small Animal Practitioner. 2nd ed. Jackson: Teton NewMedia, 2004.

NOCICEPTION

Perception: opioids, α2 agonists

Modulation: local anesthetics, opioids, NMDA

antagonists, α2 agonists, NSAIDs

Transmission: local anesthetics, α2 agonists

Transduction: local anesthetics, opioids, NSAIDs

SYSTEMIC OPTIONS

Injectable

CRIs

Oral

Non-CII Opiates

Alpha 2 agonists

NMDA antagonists

Na channel blockers

NK 1 receptor antagonist

Tramadol

NSAIDs and PRAs

Acetaminophen

Gabapentin/Trazadone

Butorphanol and Nalbuphine

mu antagonist, kappa agonist

Butorphanol less analgesia than compared to NSAIDS1

Butorphanol better acute visceral than somatic in cats2

CIVClinical Applications IV IM SQ

Butorphanol (CIV) Nalbuphine2 (not controlled)

0.1-0.4 mg/kg 3 mg/kg

CRI 0.1-0.2 mg/kg/h

Duration 45 min-1.5 h Duration 1.5-2 h

BUPRENORPHINE [0.3 mg/ml]

Partial mu agonist

0.01-0.04 mg/kg cats and dogs

6-12 h duration IV, IM, SQ

Buprenorphine + NSAID1,2

IV or oral transmucosal in cats-best3,4

CIIIClinical Applications IV IM SQ PO

OTHER BUPRENORPHINE FORMULATIONS

CIIIClinical Applications SQ

Simbadol Buprenorphine SR2,3

1.8 mg/mL, preserved sol’n; multidose

vial

Various strengths; preserved?

FDA approved Compounded; not FDA approved

Dose rate: 0.24 mg/kg SC; for 3

consecutives days

Dose rates:

Cats: 0.12 mg/kg

Dogs: up to 0.06 mg/kg

Rats: up to 1.2 mg/kg

Mice: up to 1 mg/kg (once)

Onset 1 h and duration of effect 24 h Purported duration of effect 72 h

ALPHA2 AGONISTS

Profound sedation

Muscle relaxation

Analgesia

Side effects: hyperglycemia,

urination, vomiting and cardiovascular effects

Clinical Applications IV IM

Dexmedetomidine

Medetomidine

Xylazine1

Atipamezole

SQ

KETAMINE

Dissociative anesthetic

NMDA antagonist

Somatic analgesia1 (integumentary and superficial musculoskeletal)

Prevents windup or hyperalgesia2

Sub-anesthetic doses (3-20 g/kg/min)

Local infiltration-brief effect, doubles bupivacaine's duration3

Use in epidural w/ or w/o other drugs

1.Clinical Applications IV IM SQ

KETAMINE CONTINUED

1.

Dogs administered ketamine infusions had

significantly lower pain scores 12 and 18 h

after surgery

Dogs were significantly more active on

post-op day 3 than saline group

Clinical Applications IV IM SQ

CIII

PAIN

AMANTIDINE

Developed as an antiviral drug for humans

Mechanism of action NMDA antagonist

Prevent wind-up in cats1

Better w/ meloxicam for OA in dogs2

Dosages:

Dogs 3-5 mg/kg PO q12-24 h2

Cats 2 mg/kg PO q 24 h3

1.Clinical ApplicationsNot

FDA

LIDOCAINE

Cough suppression1

CRISoft tissue2

Orthopedic/Neuro

intra-ocular3

Other useful effects4-6

Inhibits endotoxin release

Free radical scavenger

Anti-inflammatory

Antimicrobial activity

1.Clinical Applications IV IM SQ

LIDOCAINE CONTINUED

Sodium channel blocker

Caution: cats, 3° AV block or sick sinus syndrome, liver disease

1.

Species Clinical

Dose

Toxic Dose

(Healthy1)

GI effects Cardiovascular

effects

CNS

effects

Seizures

3 mg/kg 12 mg/kg Nauseous

Vomiting

Initial increase

in HR, BP and

CO with CNS

excitation,

followed by

decrease in HR,

BP and CO,

progressive

ventricular

arrhythmias,

fibrillation and

cardiac arrest

Muscle

twitches,

weakness,

convulsions

22 mg/kg

2 mg/kg 6 mg/kg 11.7+4.6

mg/kg2

MAROPITANT (Cerenia®)

FDA approved antiemetic for dogs and cats

Visceral analgesic properties1,2

1 mg/kg IV = 15% MAC ↓1 1 mg/kg, 30 g/kg/h = 24% MAC ↓2

TRAMADOL

M1-Weak mu agonist, inhibits norepinephrine and serotonin reuptake

Caution with SSRI, MAOI or tricyclic antidepressants

Dogs: large individual variability, variable clinical effects

Bupivicaine & maropitant inhibit M1 formation. 1,2

Cats >M1 = More opioid effects3

Not sole analgesic

Administered with NSAID5,6,7,8

+/- proton pump inhibitor9

Not FDA approved for veterinary use1.Clinical Applications CIV

Not

FDA

Non-Steroidal Anti-InflammatoryDrugs (NSAIDs)

NSAID Labeled

Species*

Cox1

inhibition

Cox2

inhibition

Dose (product inserts)

Ketoprofen Horses (US)

Dogs (Canada)

+++ + Dogs: 2 mg/kg SC, IM 1st dose, 1 mg/kg PO, SQ following SID

Cats: 1 mg/kg SC, IM 1st dose, 0.5 mg/kg PO, SQ following SID

Meloxicam

(Metacam)

Cats

Dogs

+ +(+) Cats: black box warning, single dose SQ 0.3 mg/kg >4mos

Dogs: SC or IV > 6 mos, 1st dose 0.2 mg/kg, q24h 0.1 mg/kg oral

suspension

Carprofen

(Rimadyl)

Dogs

Cats (not US)

+ +(+) Dogs: 2.2 mg/kg BID or 4.4 mg/kg SID >6 weeks Oral Tab or SC

injection

Dexacoxib

(Deramaxx)

Dogs + ++ Dogs: 1-4 mg/kg/day as single dose <7 days, >4 months of age

Robenacoxib

(Onsior)

Cats

Dogs

+ +++ Cats: (tab) 1mg/kg SID max 3 days, (injection) 2 mg/kg SID SC max 3

days

Dogs: (tab or inject) 2 mg/kg SC/PO SID max. 3 days

Firocoxib

(Previcox)

Dogs + +++ 5 mg/kg daily tablets

GALLIPRANT – 1st IN CLASS

Prostaglandin receptor antagonist (PRA)

Dogs, > 9 months with OA1

2 mg/kg, PO SID

Do not co-administer with NSAIDs or Corticosteroids

Arachidonic Acid

5H PETE Prostaglandins

PGE2

Inflammation

Mucosal

defenseRenal

ProtectionPlt

Function

COX 1 COX 2

TXA2PGI2

InducibleConstituent

5-LOX

Inducible

LTD4

G

EP4

ACETAMINOPHEN (TYLENOL®)

AKA Paracetamol

Mechanism of action still poorly understood

Analgesic and antipyretic, not anti-inflammatory

DO NOT USE IN CATS!

Sold in combination with codeine, oxycodone and hydrocodone

Dogs: 10-15 mg/kg PO q 8-12 h

1.Clinical ApplicationsNot

FDA

THERAPUEUTICS

Gabapentin Trazodone

Atypical antidepressant

SARI

Caution with other SSRIs

The drug produces sedation/anxiolysis2,3

Dogs: 3.5 mg/kg PO q12h

Cats: 25-100 mg/cat PO4

1.Clinical ApplicationsNot

FDA

Indicated for seizures

MOA – Ca channels in CNS

Treatment of neuropathic pain1

Sedation for fractious cats

10-20 mg/kg PO

Chronic use gradually withdraw

CONSTANT RATE INFUSIONS

Advantages:

Continuous infusion minimal break through

Low doses = reduced side effects

Titratable

Disadvantages:

Compatibility of drugs

Stability

Mathematics

CRI RATE SUGGESTIONS

Drug Loading Dose (IV) Anesthesia CRI (IV) Comments

Hydromorphone 0.025-0.05mg/kg 0.01-0.04 mg/kg/h 0.01-0.02 mg/kg/h post-op

Morphine 0.1-0.3 mg/kg 0.1-0.3 mg/kg/h give loading dose slow IV

Methadone 0.1 mg/kg 0.1 mg/kg/h

Fentanyl 2-5 mcg/kg 2-40 mcg/kg/h 1-5 mcg/kg/h post-op

Remifenanil 2-5 mcg/kg 2-40 mcg/kg/h 1-5 mcg/kg/h post-op

Sufentanil 0.25-2 mcg/kg 0.5-2 mcg/kg/h 0.25-1mcg/kg/h post-op

Butorphanol 0.1-0.2 mg/kg 0.1-0.2 mg/kg/h Poor analgesia, good

sedation

Lidocaine 0.5-2 mg/kg 1-3 mg/kg/h Caution in cats

Ketamine 0.3-1 mg/kg 0.12-1.2 mg/kg/h 0.12-0.3 mg/kg/h post-op

Dexmedetomidine 0.5-1 mcg/kg 0.25-3 mcg/kg/h

Medetomidine 1-5 mcg/kg 1-5 mcg/kg/h

CRI SOLUTION FORMULA

Dosage

Fluid Rate× total volume = mg of drugs

mg of drug ×1

Concentration= ml of drugs to add

Reminders:

-Stock solution

-Rate of delivery influenced by patient weight

Golden rule of calculations = units must cross cancel

Dose mg/kg/h X ml

Fluid rate ml/kg/h

mg X ml

mg

CRI EXAMPLE

Dosage

Fluid Rate× total volume = = 600mg of Lidocaine

mg of drug ×1

Concentration= 30ml of drugs to add

Reminders:

-remove 30 ml from fluid bag, then add drug

-calculate drip rate or ml/h to deliver to specific pt.

-label bag contents

-no bolus of fluids

Lidocaine 3 mg/kg/h X 1000 ml

Fluid rate 5 ml/kg/h

600 mg X 1 ml

20 mg

PATIENT DELIVERY

Anesthesia fluid rate used in equation:

Pt. (kg) X Fluid Rate (5 mL/kg/h) = ml/h

Post-op Maintenance:

2.5 mL/kg/h = reduced

Lidocaine to 1.5 mg/kg/h

Lidocaine

in

Fluids

RECAP

Part 1 Completed

Systemic Options

Injectable and Oral

Calculating CRIs

Part 2

Local Analgesics and Adjuvants

Methods and Calculations

Loco-Regional Techniques

Example protocols